Improved synthesis of an ester-type prodrug, 1-acetoxyethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-[(Z)-1- propenyl]-3-cephem-4-carboxylate (BMY-28271).
1-Acetoxyethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3- [(Z)-1-propenyl]-3-cephem-4-carboxylate (BMY-28271) is an ester-type prodrug of cephalosporin for oral use. Methods suitable for large scale preparation were investigated. The yield was improved by esterification of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-trityloxyiminoacetamido]cep hem-4-carboxylic acid (11) followed by removal of the trityl group and, in addition, column chromatographic purification at each step was eliminated by optimization of the reaction conditions.
Kamachi
H
H
Bristol-Myers Squibb Research Institute, Tokyo, Japan.
Okita
T
T
Okuyama
S
S
Hoshi
H
H
Naito
T
T
D000215:Acylation; D002511:Cephalosporins / Q000138:chemical synthesis*; D002855:Chromatography, Thin Layer; D004952:Esters; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis*
D002511:Cephalosporins; D004952:Esters; D011355:Prodrugs; C060354:BMY 28271